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Valentijn, K.M.; Driel, L.F. van; Mourik, M.J.; Hendriks, G.J.; Arends, T.J.; Koster, A.J.; Valentijn, J.A. (2010)

Multigranular exocytosis of Weibel-Palade bodies in vascular endothelial cells

Article / Letter to editor
Regulated exocytosis of Weibel-Palade bodies (WPBs) is a pivotal mechanism via which vascular endothelial cells initiate repair in response to injury and inflammation. Several pathways have been proposed to enable differential release of bioactive molecules from WPBs under different pathophysiologic conditions. Due to the complexity, many aspects of WPB biogenesis and exocytosis are still poorly understood. Herein, we have investigated the regulated exocytosis of the major WPB constituent, von Willebrand Factor (VWF), which upon its release forms strings of up to several millimeters long that capture circulating platelets and thereby initiate the formation of a haemostatic plug. Using correlative, fluorescence, and electron microscopic imaging techniques, we provide evidence that multigranular exocytosis is an important pathway for VWF release in secretagogue-challenged human umbilical vein endothelial cells. A novel membrane-delimited structure (secretory pod) was identified as the...Show moreRegulated exocytosis of Weibel-Palade bodies (WPBs) is a pivotal mechanism via which vascular endothelial cells initiate repair in response to injury and inflammation. Several pathways have been proposed to enable differential release of bioactive molecules from WPBs under different pathophysiologic conditions. Due to the complexity, many aspects of WPB biogenesis and exocytosis are still poorly understood. Herein, we have investigated the regulated exocytosis of the major WPB constituent, von Willebrand Factor (VWF), which upon its release forms strings of up to several millimeters long that capture circulating platelets and thereby initiate the formation of a haemostatic plug. Using correlative, fluorescence, and electron microscopic imaging techniques, we provide evidence that multigranular exocytosis is an important pathway for VWF release in secretagogue-challenged human umbilical vein endothelial cells. A novel membrane-delimited structure (secretory pod) was identified as the site of WPB coalescence and VWF exocyto-sis. Clathrin-coated profiles present on the secretory pods suggested remodeling via compensatory membrane retrieval. Small, 30- to 40-nm cytoplasmic vesicles (nanovesicles) mediated the fusion of WPBs with secretory pods. Multigranular exocytosis may facilitate VWF string formation by pooling the content of multiple WPBs. In addition, it may provide a novel mechanism for the differential release of WPB cargo. (Blood. 2010;116(10):1807-1816)Show less
von-willebrand-factor protein-kinase-c vonwillebrand-factor platelet-adhesion body exocytosis de-granulation acinar-cells secretion release biogenesis
All authors
Valentijn, K.M.; Driel, L.F. van; Mourik, M.J.; Hendriks, G.J.; Arends, T.J.; Koster, A.J.; Valentijn, J.A.
Date
2010-09-09
Journal
Blood
Volume
116
Issue
10
Pages
1807 - 1816
DOI
doi:10.1182/blood-2010-03-274209